1. Field of the Invention
The present invention relates to preparing therapeutics of an injectable solution containing carvacrol and thymol isolated from natural origins for intramuscular or intravenous application in the form of an organic complex compounded with pharmacological base agents for use in human and veterinary medicine.
2. Description of Related Art
Treatment of infectious diseases is primarily done with antibiotics, sulfonamides, steroid hormones, antifungal, and antiprotozoan compounds. Viral infections are more difficult to treat and limited drugs are available that treat them without significant side effects. In the case of bacterial and fungal disease, an increasing problem is the numbers of resistant and multi-drug resistant organisms. These necessitate the use of antimicrobial drugs that have more toxic side effects that can often lead to liver and kidney damage. Thus, the development of antimicrobial compounds from natural sources, such a medicinal herbs or plants, is an advantageous solution that addresses some of these concerns. The Lamiaceae and Labiatae families of plants are known to have useful medicinal properties. The related Verbenaceae family of plants also has similar medicinal characteristics.
The common name for members of the Labiatae, a large family of chiefly annual or perennial herbs, is the “mint family.” The mint family is classified in the division Magnoliphyta, class Magnoliopsida, order Lamiales. The mint family includes about 200 genera, such as Salvia (sage), Rosmarinus (rosemary), Mentha (mint), Ocimum (basil), Thymus (thyme), Marrubium (hoarhound), Monarda (horse mint), Trichostema (bluecurls), Teucrium, Hyptis, Physostegia, Lamium (henbit), Stachys, Scutellaria (skullcap), Nepeta (catmint). Members of the Verbenaceae family include Lippia (Mexican Oregano) and Lycopus. The plants in the mint family are typically shrubby or climbing, although some exist as small trees. The plants are found throughout the world.
The mint family is well known for the aromatic volatile or essential oils in the foliage, which are used in perfumes, flavorings, and medicines. Among the more important essential oils are those derived from sage, lavender, rosemary, patchouli, and the true mints. Many of the commonly used herbs are from the mint family, e.g., basil, thyme, savory, marjoram, oregano, and the like.
Many of these plants such as catnip, pennyroyal, hyssop, self-heal, and the horehound of confectionery have a history of medicinal use in domestic remedies. Others are used as curative teas, for example, bee balm and yerba Buena.
The true mints belong to the genus Mentha. Catnip or catmint refers to a strong-scented perennial herb (Nepeta cataria) of the family Labiatae. Catnip is native to Europe and Asia and naturalized in the United States. Although best known for its stimulating effect on cats, tea of the leaves and tops of the catnip plant have long been used as a domestic remedy for various ailments. For example, dry leaves from Nepeta cataria have been used for the production of tea, to treat restlessness, nervousness, insanity, and as a tonic for colic and carminative.
Members of the Lamiaceae, Labiatae, and Verbenaceae families of plants contain two chemical compounds in their volatile oils that have antimicrobial activities, and are commonly referred to as carvacrol (5-isopropyl-2-methylphenol or isopropyl-o-cresol) and thymol (5-methyl-2[1-methylethyl]phenol or isopropyl-cresol). These both are monoturpene phenolic compounds and are potent antimicrobial agents. They are effective against bacteria, fungi, and protozoan pathogens. Furthermore, it is believed that they kill these organisms by disrupting their cellular membranes and do not select resistant members of these pathogens. They are also not toxic for animals, including humans, and have been used in natural herb form or in oil preparations from these plants for many centuries. The development of a broad spectrum antimicrobial compound is important given the increasing problems with antibiotic resistant organisms including bacteria, yeast, fungi, and protozoan species.
The antimicrobial activity of carvacrol and thymol containing compounds is recognized by people skilled in the art and been developed for use in birds and animals. For example, U.S. Pat. No. 5,990,178 discloses pharmaceutical compositions for treating a disease in poultry induced by hemoflagellates. The pharmaceutical compositions disclosed therein contain the monoturpene phenolic compounds carvacrol and thymol. Both of these compounds are can be synthetic or obtained from oil extract from plants such as Origanum vulgaris, Thymus vulgaris, Mentha piperita, Thymus sepilum, Saturia hortensis, Saturea montana, Saturea subricata, Carum corticum, Thymus zugus, Ocimum gratisimum, Moranda pungata, Mosla jananoica, and Salva off cinalis. The '718 patent shows that the carvacrol and thymol are effective in treating a histomoniasis protozoan infection in various birds. A problem exists in that such monoturpene phenolic compounds may cause irritation and pain and so are not well suited for use in humans.
Also, U.S. Pat. No. 6,322,825 discloses pharmaceutical compositions for treating gastrointestinal infections in animals. The pharmaceutical compositions disclosed therein contain carvacrol and/or thymol. Thymol and carvacrol which can be synthetic or obtained from plant oil extracts, such as Origanum vulgaris, Thymus vulgaris, Mentha piperita, Thymus sepilum, Saturia hortensis, Saturea montana, Saturea subricata, Carum corticum, Thymus zugus, Ocimum gratisimum, Moranda pungata, Mosla jananoica, and Salva off cinalis. In the '825 patent the use of the antimicrobial agents use is extended showing that the carvacrol and thymol containing compounds are effective against a large number of bacterial and fungal species. The application of such compounds is likely to result in significant gastrointestinal distress in humans precluding there use as therapeutic agents.
The U.S. Pat. No. 6,414,036 discloses compositions of carvacrol (isopropyl-o-cresol) and thymol (isopropyl-cresol) combined with Group I salts or organic acids that have antimicrobial activity. The compounds are effective against a broad number of bacterial, yeast, fungal, and protozoan species. Furthermore, the compounds are believed to have enhanced antimicrobial activity due to the reaction with Group I salts or organic acids. The compounds are proposed for use primarily in animal livestock, but also are proposed for use in humans. Despite the description of enhanced antimicrobial activity these compounds are still likely to cause irritation, pain, and distress when used in humans at therapeutic levels. The significant issue of pain and discomfort that are often associated with the use of monoturpene phenolic compounds based on carvacrol and thymol must be addressed to provide effective and useful human therapeutic compounds.
The application of such carvacrol and/or thymol compounds in therapies for human medicine must overcome certain problems that are less important in veterinary uses. One major concern is the irritation, discomfort, and pain that can result from the injection of monoturpene phenolic compounds, such as carvacrol and thymol. It is desirable to have an injectable formulation of carvacrol and thymol for treatment of internal human infections that is effective and does not cause pain or discomfort. Such a drug is also useful for veterinary medicine. An injectable agent allows treatment of internal infections in a quick timely manner that increases the chances of recovery. The dose of antimicrobial compound is also more constant and can be maintained better at therapeutic levels easier in an injectable form. If left unchecked or if treatment is slow, microbial infections can result in death even when effective conventional therapies are employed. Therefore, it would be desirable to provide an injectable form of carvacrol and thymol to achieve a more effective, pleasing, and reliable way to deliver the antimicrobial agents in doses that can be sustained over the time required to treat infectious diseases.